Temporary interruption of warfarin therapy for an elective surgical or other invasive procedure is a common clinical problem, affecting ~400,000 patients in North America annually. Increasingly, clinicians employ a low molecular weight heparin (LMWH) as a 'bridge' before and after surgery or a procedure, when warfarin is withheld and anticoagulation is otherwise sub-therapeutic. This empiric strategy has several drawbacks, including lack of proven efficacy to prevent arterial thromboembolism, additional cost to the healthcare system, and the potential for increased peri-operative bleeding. Unfortunately, there are no high-quality clinical trials to provide Level 1A evidence to guide patient care. We hypothesize that simply withholding warfarin in the perioperative setting for patients with atrial fibrillation will not meaningfully increase the risk for arterial thromboembolism, and will forestall hemorrhagic complications, compared to a strategy using LMWH before and after surgery. To address this important question, we propose a multi-center, prospective, double-blind, placebo-controlled randomized clinical trial that randomly allocates 3,282 patients with atrial fibrillation to either therapeutic dose LMWH or matching placebo before and after surgery (1641 patients per arm). Forty enrolling centers in North America will recruit over 44 months. Exclusion criteria include: mechanical heart valve; recent stroke or major bleed; severe renal insufficiency, thrombocytopenia; or planned surgery that precludes use of post-operative therapeutic-dose LMWH. Primary efficacy outcome is arterial thromboembolism (stroke, TIA, or systemic embolism), and primary safety outcome is major bleeding (symptomatic, clinically-overt, or fatal). We will conduct a non-inferiority efficacy analysis to demonstrate that "no bridging" has a risk for arterial thromboembolism equal to a bridging strategy. Clinical outcomes will be analyzed using the per protocol population for the efficacy outcome and the intention-to-treat population for the safety endpoint. Dissemination of trial results will target physicians and other providers who manage patients with atrial fibrillation on chronic warfarin therapy. This randomized trial comparing bridging therapy to a "no bridging" strategy will establish a clear standard-of-care for the management of these patients. This application is in companion application to the Statistical Data Coordinating Center submitted separately. [unreadable] [unreadable] Clinicians frequently use low-molecular weight heparin as a 'bridge' before and after an elective procedure for patients on chronic warfarin therapy. It is unknown if this practice is efficacious, however, and it may actually result in an increased risk for periprocedural hemorrhage. This prospective, randomized, double-blind study will definitively answer this question for patients with atrial fibrillation who are on warfarin therapy. [unreadable] [unreadable] [unreadable]